Article
Biochemistry & Molecular Biology
Yang Liu, Qian Liu, Handong Su, Kunpeng Liu, Xue Xiao, Wei Li, Qianwen Sun, James A. Birchler, Fangpu Han
Summary: The study identified over 700,000 R-loop peaks in the maize genome, with sense R-loops mainly enriched in promoters and transcription termination sites. At the chromosome scale, maize R-loops were enriched in pericentromeric heterochromatin regions.
Review
Biochemistry & Molecular Biology
Joshua R. Brickner, Jada L. Garzon, Karlene A. Cimprich
Summary: R-loops, non-B DNA structures formed during transcription, can cause genomic instability but also have regulatory roles in maintaining genome integrity. They contribute to genomic instability during DNA replication and double-strand break repair, but also participate as intermediates in repair and influence pathway choice. Additionally, R-loops may be linked to disease.
Review
Biochemistry & Molecular Biology
Noha Elsakrmy, Haissi Cui
Summary: R-loops are three-stranded DNA/RNA hybrids that can regulate gene expression and DNA damage response. Imbalanced R-loop formation can lead to cancer progression and drug resistance. Understanding the interplay between R-loops and tumor suppressors and oncogenes can provide insights into novel cancer therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Magdalena P. Crossley, Joshua R. Brickner, Chenlin Song, Su Mon Thin Zar, Su S. Maw, Frederic Chedin, Miaw-Sheue Tsai, Karlene A. Cimprich
Summary: The study focused on imaging R-loop structures, highlighting the issues with using the S9.6 antibody and proposing GFP-dRNH1 as a more specific imaging reagent that can effectively bind to RNA-DNA hybrids without binding to dsRNA oligonucleotides and being susceptible to endogenous RNA interference. Purified GFP-dRNH1 can be used to detect RNA-DNA hybrids in fixed cells, bypassing the need for cell line engineering.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Phillip Wulfridge, Qingqing Yan, Nathaniel Rell, John Doherty, Skye Jacobson, Sarah Offley, Sandra Deliard, Kelly Feng, Jennifer E. Phillips-Cremins, Alessandro Gardini, Kavitha Sarma
Summary: CTCF is a critical regulator of genome architecture and gene expression. This study shows that R-loops and G-quadruplex structures facilitate CTCF binding and regulate chromatin organization. The stability of R-loops and G-quadruplex structures can affect CTCF occupancy and gene expression.
Article
Chemistry, Multidisciplinary
Sumon Pratihar, Mohamed Nabeel Mattath, Thimmaiah Govindaraju
Summary: Pathogenic genomes with noncanonical G-quadruplex (GQ) forming sequences are potential targets for diagnosis. The GQ-forming cDNA sequences of SARS-CoV-2 have been identified and validated as reliable diagnostic targets. High fidelity fluorescence detection of specific cDNA GQs derived from the SARS-CoV-2 RNA genome is demonstrated using small molecular probes.
CHEMICAL COMMUNICATIONS
(2023)
Article
Cell Biology
Esther Marchena-Cruz, Lola P. Camino, Jay Bhandari, Sonia Silva, Jose Javier Marqueta-Gracia, Shahad A. Amdeen, Cristina Guillen-Mendoza, Maria L. Garcia-Rubio, Jose M. Calderon-Montano, Xiaoyu Xue, Rosa Luna, Andres Aguilera
Summary: Unscheduled R loops can lead to genome instability, a characteristic of cancer cells. By targeting activation-induced cytidine deaminase (AID), 59 potential candidates causing R loops were identified, which are enriched in factors involved in chromatin, transcription, RNA biogenesis, and other processes. The study suggests that various gene dysfunctions can affect R-loop homeostasis through different mechanisms, thereby altering cell physiology.
Review
Biochemistry & Molecular Biology
Frederic Chedin, Stella R. Hartono, Lionel A. Sanz, Vincent Vanoosthuyse
Summary: R-loops are a class of large non-B DNA structures in genomes, forming transiently and at modest frequencies, yet impacting genome stability significantly. The mechanisms of R-loop-mediated genome destabilization require precise characterization of their distribution in genomes. The discordant results from different mapping methods highlight the need for best practices to improve reproducibility in mapping these structures.
Review
Oncology
Fang Li, Alyan Zafar, Liang Luo, Ariana Maria Denning, Jun Gu, Ansley Bennett, Fenghua Yuan, Yanbin Zhang
Summary: R-loops are three-stranded structures consisting of an RNA-DNA hybrid and an unpaired single-stranded DNA, with biological implications in cellular physiology and pathological conditions. The accumulation of R-loops is associated with the development of various types of cancer, and studying their roles in cancer development is of great significance for innovative diagnostic and treatment approaches for cancer.
Review
Biochemistry & Molecular Biology
Veronica Marabitti, Pasquale Valenzisi, Giorgia Lillo, Eva Malacaria, Valentina Palermo, Pietro Pichierri, Annapaola Franchitto
Summary: Maintenance of genome stability is crucial for cell survival, which relies on accurate DNA replication. Transcription poses as a major threat to DNA replication, as collisions between the two processes occur frequently. R-loops, which consist of a DNA-RNA hybrid and displaced single-stranded DNA, are the main harmful structures associated with transcription. When their homeostasis is disturbed, R-loops become a potent source of replication stress and genome instability, leading to various human diseases including cancer. Cells have evolved multiple mechanisms to combat the deleterious consequences of R-loop persistence, and several replication fork protection factors have been implicated in preventing/removing these harmful structures.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Vaclav Brazda, Jan Havlik, Jan Kolomaznik, Oldrich Trenz, Jiri Stastny
Summary: R-loops, formed by RNA-DNA hybrid and displaced single-stranded DNA, are common non-B nucleic acid structures that play important roles in human diseases by promoting mutagenesis, hyper-recombination, and transcription-replication collisions. To better study and predict R-loops, researchers have developed the R-loop tracker tool, integrating it with other nucleic acids analysis tools and enhancing visualization outputs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Marta San Martin Alonso, Sylvie M. Noordermeer
Summary: R-loops, RNA:DNA hybrids, play crucial roles in DNA repair processes, but excessive R-loop formation is linked to genetic instability. The multifaceted BRCA1 protein is recruited at DNA double-strand breaks to regulate R-loop removal, ensuring faithful repair processes.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Hun-Goo Lee, Sachiko Imaichi, Elizabeth Kraeutler, Rodrigo Aguilar, Yong-Woo Lee, Steven D. Sheridan, Jeannie T. Lee
Summary: In this article, we describe an approach to correct the genetic defect in fragile X syndrome (FXS) through the recruitment of endogenous repair mechanisms. By investigating conditions favorable to FMR1 reactivation, we identify MEK and BRAF inhibitors that induce a strong repeat contraction and full FMR1 reactivation in cellular models. This study reveals a potential method of treating FXS in the future by recruiting endogenous DNA repair mechanisms.
Correction
Cell Biology
Carmen Perez-Calero, Aleix Bayona-Feliu, Xiaoyu Xue, Sonia I. Barroso, Sergio Munoz, Victor M. Gonzalez-Basallote, Patrick Sung, Andres Aguilera
Summary: In the process of preparing Supplemental Figure S7D for the final version of the article, two of the DRIPc-seq profiles were unintentionally plotted with a different bin size. The amended version of the figure has been marked with RNH-sensitive regions and can be found in the Revised Supplemental Material online. The revised plots correspond to the original data and do not change the conclusions of the paper.
GENES & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Natalie Laspata, Parminder Kaur, Sofiane Yacine Mersaoui, Daniela Muoio, Zhiyan Silvia Liu, Maxwell Henry Bannister, Hai Dang Nguyen, Caroline Curry, John M. Pascal, Guy G. Poirier, Hong Wang, Jean-Yves Masson, Elise Fouquerel
Summary: PARP1 is a DNA-dependent ADP-Ribose transferase that is involved in resolving DNA breaks and non-B DNA structures. It has been identified as a component of the R-loop-associated protein-protein interaction network, suggesting its potential role in resolving R-loop structures. R-loops are three-stranded nucleic acid structures that can cause genome instability if persistently unresolved.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Medicinal
Xiangping Deng, Baohua Xie, Qiuzi Li, Yuan Xiao, Zhiye Hu, Xiaofei Deng, Pingping Fang, Chune Dong, Hai-Bing Zhou, Jian Huang
Summary: This study identified a new ER modulator, 34b, which showed antiproliferative effects against breast cancer cells and induced apoptosis through mitochondrial dysfunction. In vivo experiments demonstrated that 34b had better tumor suppression than tamoxifen. Therefore, this compound has potential as a candidate for treating breast cancer, particularly tamoxifen-resistant breast cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Fangliang Zhang, Liang Chen
Summary: Splicing factor mutations play a significant role in MDS and AML, but their underlying mechanisms are not fully understood. Although specific treatment options are currently unavailable, novel targeting strategies are being explored, with potential clinical benefits for patients with splicing factor mutations.
Article
Multidisciplinary Sciences
Xiaoyu Wei, Sulei Fu, Hanbo Li, Yang Liu, Shuai Wang, Weimin Feng, Yunzhi Yang, Xiawei Liu, Yan-Yun Zeng, Mengnan Cheng, Yiwei Lai, Xiaojie Qiu, Liang Wu, Nannan Zhang, Yujia Jiang, Jiangshan Xu, Xiaoshan Su, Cheng Peng, Lei Han, Wilson Pak-Kin Lou, Chuanyu Liu, Yue Yuan, Kailong Ma, Tao Yang, Xiangyu Pan, Shang Gao, Ao Chen, Miguel A. Esteban, Huanming Yang, Jian Wang, Guangyi Fan, Longqi Liu, Liang Chen, Xun Xu, Ji-Feng Fei, Ying Gu
Summary: This study used Stereo-seq technology to analyze spatial distribution and molecular features of axolotl brain during development and regeneration. The researchers identified an injury-induced ependymoglial cell cluster as a potential progenitor cell population for replenishing lost neurons. They also discovered regressed neurons and provided evidence for the involvement of resident ependymoglial cells in neurogenesis.
Article
Hematology
Yi-Jou Huang, Jia-Yu Chen, Ming Yan, Amanda G. Davis, Sayuri Miyauchi, Liang Chen, Yajing Hao, Sigrid Katz, Rafael Bejar, Omar Abdel-Wahab, Xiang-Dong Fu, Dong-Er Zhang
Summary: This study presents a mouse model and a cellular model to demonstrate how alterations in transcription and splicing collectively contribute to the development of MDS in a double mutant.
Editorial Material
Oncology
Xiaoyu Wei, Hanbo Li, Jiaxin Du, Xiaoqi Zeng, Xun Xu, Liang Chen, Ying Gu
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Medicinal
Baohua Xie, Zhinang Yin, Zhiye Hu, Junhui Lv, Chuanqian Du, Xiangping Deng, Yuan Huang, Qiuzi Li, Jian Huang, Kaiwei Liang, Hai-Bing Zhou, Chune Dong
Summary: This study reveals a novel series of potent ER alpha PROTACs based on the OBHSA scaffold, showing significant antiproliferation and ER alpha degradation activities against a broad spectrum of ER+ BC cells. Compound ZD12 exhibits excellent antitumor potency and ER alpha degradation activity, making it a promising drug candidate for endocrine-resistant BC treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Donghai Wang, Zhinang Yin, Honghong Wang, Liyuan Wang, Tianyu Li, Ruijing Xiao, Ting Xie, Ruyi Han, Rui Dong, Hudan Liu, Kaiwei Liang, Guoliang Qing
Summary: MYCN amplification in neuroblastoma leads to aberrant expression of MYCN oncoprotein, which activates active genes and enhances transcriptional elongation. Super elongation complex (SEC) is identified as a vulnerability in MYCN-amplified neuroblastomas and is recruited by MYCN to enhance processive transcription elongation. Inhibition of SEC leads to global reduction in transcription elongation and selective apoptosis of MYCN-amplified neuroblastoma cells, and synergistically enhances the therapeutic efficacy of BCL-2 antagonist ABT-199 in MYCN-amplified neuroblastomas.
Article
Multidisciplinary Sciences
Min Qiu, Zhinang Yin, Honghong Wang, Lingyu Lei, Conghui Li, Yali Cui, Rong Dai, Peiyuan Yang, Ying Xiang, Qiuzi Li, Junhui Lv, Zhuang Hu, Min Chen, Hai-Bing Zhou, Pingping Fang, Ruijing Xiao, Kaiwei Liang
Summary: The study reveals that Cyclin-dependent kinase 12 (CDK12) interacts with cyclin K to promote transcription elongation. Using chemical genetic and phosphoproteomic screening, a landscape of CDK12 substrates including regulators of transcription, chromatin organization, and RNA splicing was identified. LEO1, a subunit of the polymerase-associated factor 1 complex (PAF1C), was validated as a cellular substrate of CDK12, and its phosphorylation was found to be regulated by the Integrator-PP2A complex (INTAC).
Article
Multidisciplinary Sciences
Congling Xu, Chengyu Li, Jiwei Chen, Yan Xiong, Zhibin Qiao, Pengyu Fan, Conghui Li, Shuangyu Ma, Jin Liu, Aixia Song, Bolin Tao, Tao Xu, Wei Xu, Yayun Chi, Jingyan Xue, Pu Wang, Dan Ye, Hongzhou Gu, Peng Zhang, Qiong Wang, Ruijing Xiao, Jingdong Cheng, Hai Zheng, Xiaoli Yu, Zhen Zhang, Jiong Wu, Kaiwei Liang, Yan-Jun Liu, Huasong Lu, Fei Xavier Chen
Summary: The stable interaction between genome stability regulator SOSS and transcription regulator INTAC is discovered. SOSS-INTAC promotes promoter-proximal termination of transcription and reduces R-loop accumulation associated with paused RNA polymerase II to prevent R-loop-induced genome instability. The condensate formation ability of SSB1 enhances the SOSS-INTAC-dependent attenuation of R-loops. Deletion of NABP2 or cancer-associated mutations in the intrinsically disordered region of SSB1 leads to widespread R-loop accumulation, highlighting the genome surveillance role of SOSS-INTAC in timely termination of transcription to ensure genome stability.
Article
Biotechnology & Applied Microbiology
Conghui Li, Zhinang Yin, Ruijing Xiao, Beili Huang, Yali Cui, Honghong Wang, Ying Xiang, Lingrui Wang, Lingyu Lei, Jiaqin Ye, Tianyu Li, Youquan Zhong, Fangteng Guo, Yuchen Xia, Pingping Fang, Kaiwei Liang
Summary: This research discovered that G4 can function as a sensor for natural porphyrin metabolites in cells, revealing a new G4-dependent mechanism for metabolic regulation of gene transcription and chromatin landscapes.